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Immunoreactive interleukin-6 and acute phase proteins as prognostic factors
in multiple myeloma. Finnish Leukemia Group
TT Pelliniemi, K Irjala, K Mattila, K Pulkki, A Rajamaki, A Tienhaara, M Laakso and R Lahtinen
Department of Hematology, Turku University Central Hospital, Finland.
High serum level of bioactive interleukin-6 (IL-6) is regarded as a
predictor of poor prognosis in multiple myeloma (MM). On the other hand,
the reported levels of immunoreactive IL-6 have been highly variable, and
the prognostic value of immunoreactive IL-6 in MM is not clear. We have
analyzed the prognostic significance of serum immunoreactive IL-6, as
measured by a sensitive immunosorbent assay, in 210 patients with newly
diagnosed MM subsequently treated with intermittent melphalan and
prednisone. The serum levels of acute phase proteins C-reactive protein
(CRP), alpha 1-antitrypsin (alpha 1AT), and acid alpha 1-glycoprotein
(orosomucoid; OM) were evaluated as surrogates for IL-6. Serum IL-6, CRP,
alpha 1AT, and OM levels were raised in 42%, 40%, 41%, and 24% of the
patients, respectively. There was a significant correlation between the
clinical stage of the patients and serum IL-6 (P = .006), alpha 1AT (P =
.001), and OM (P = .004) levels at diagnosis. At 3 years, 52% of the
patients were alive. Univariate logistic regression analysis showed that
high levels of IL-6 (P = .002), CRP (P = .02), alpha 1AT (P < .001), OM
(P = .007), beta 2- microglobulin (beta 2M; P < .001), and thymidine
kinase (P < .05) were all associated with 3-year mortality. In
multivariate regression analysis, beta 2M (P < .0001) and alpha 1AT (P =
.01) had independent prognostic significance. The patients with high levels
of both beta 2M and alpha 1AT or IL-6 were at very high risk of dying
within 3 years from diagnosis (16% and 21% of the patients in these groups
were alive, respectively). When the patients were stratified according to
the clinical stage, the prognostic significance of serum IL-6 and alpha 1AT
was especially evident in stage II patients. When the patients were divided
into two groups according to normal or raised serum IL-6 levels, the
patients with high IL-6 levels had more frequent osteolytic bone lesions (P
= .03) and a more aggressive disease. We conclude that serum immunoreactive
IL-6 is a significant prognostic marker in MM.
Volume 85,
Issue 3,
pp. 765-771,
02/01/1995
Copyright © 1995 by The American Society of Hematology
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